Pharmaceutical formulations for oral administration have employed various coatings for the purpose of preserving the integrity of the formulation while passing through the gastric tract. The high acidity, and presence of proteolytic and other enzymes generates a highly digestive environment which readily disintegrates pharmaceutical formulations which do not possess some type of gastro-resistance protection.
In recent years, a need has arisen for formulations which are capable of passing over the entire tract of the small intestine, including the duodenum, jejunum, and ileum, so that the active ingredients are released directly in the colon. For example, European Patent Application No. 366 621 provides a formulation for delivery in the colon which includes a core containing the active ingredient and three protective layers having differing solubilities around the core. As another example, our European Application No. 572 942, the disclosure of which is hereby incorporated by reference in its entirety, provides an oral pharmaceutical composition including a core containing the active ingredient, an intermediate coating layer which delays the release of the active ingredient contained in the core for a programmed time period, and an outer layer, the dissolution of which activates the process of swelling/dissolution/erosion of the intermediate layer. In the composition described in European Application No. 572 942, the coating layers are applied sequentially by watery or organic film coating or by press coating techniques, such as double press coating. A primary disadvantage of these coating methods is that these methods employ solutions of the coating polymers, which coating polymers have very high viscosities in water-based environments. The use of high viscosity polymer is advantageous because a small amount of film is sufficient to provide protection to the core. However, high viscosity polymers present an obstacle to film coating of water-based solutions because of the high viscosity. Typically, these polymers require organic solvents, or slow application procedures of very dilute water-based solutions to overcome the obstacle presented by the high viscosity of the polymers in order to successfully apply the coating agents. The use of organic solvents is not preferred because of the potential health hazards associated therewith. The use of dilute solutions also is not preferred because of the extended manufacturing times required to achieve the same degree of coating application.
Double press coating techniques have mechanical disadvantages in that the core of the formulation may not be properly centered within the coating.
It is therefore an object of the present invention to provide a method of preparing a time-specific release pharmaceutical formulation which does not require the use of organic solvents, or very dilute solutions of coating materials, and which is faster than conventional coating techniques.
There also remains a need in the art for pharmaceutical formulations which release active ingredient after a predetermined latency or lag time period in the body, i.e., time-specific release formulations.